4-80053238-A-T

Variant names:

• chr4-80053238-A-T
• rs12646132
• NM_058172.6:c.636+1034T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058172.6(ANTXR2):​c.636+1034T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,566 control chromosomes in the GnomAD database, including 2,804 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2804 hom., cov: 32)
• Consequence: ANTXR2 NM_058172.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 2 publications found

Genes affected

ANTXR2 (HGNC:21732): (ANTXR cell adhesion molecule 2) This gene encodes a receptor for anthrax toxin. The protein binds to collagen IV and laminin, suggesting that it may be involved in extracellular matrix adhesion. Mutations in this gene cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ANTXR2 Gene-Disease associations (from GenCC):

• hyaline fibromatosis syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• juvenile hyaline fibromatosis

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• infantile systemic hyalinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058172.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR2	NM_058172.6	MANE Select	c.636+1034T>A		intron	N/A	NP_477520.2	P58335-4
	ANTXR2	NM_001145794.2		c.636+1034T>A		intron	N/A	NP_001139266.1	P58335-1
	ANTXR2	NM_001286780.2		c.405+1034T>A		intron	N/A	NP_001273709.1	J3KPY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR2	ENST00000403729.7	TSL:1 MANE Select	c.636+1034T>A		intron	N/A	ENSP00000385575.2	P58335-4
	ANTXR2	ENST00000307333.7	TSL:1	c.636+1034T>A		intron	N/A	ENSP00000306185.6	P58335-1
	ANTXR2	ENST00000404191.5	TSL:1	c.405+1034T>A		intron	N/A	ENSP00000384028.1	J3KPY9

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21489 AN: 151448 Hom.: 2797 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0659

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21508 AN: 151566 Hom.: 2804 Cov.: 32 AF XY: 0.154 AC XY: 11412 AN XY: 74032

African (AFR) AF: 0.0776 AC: 3217 AN: 41482

American (AMR) AF: 0.202 AC: 3062 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 228 AN: 3462

East Asian (EAS) AF: 0.710 AC: 3603 AN: 5074

South Asian (SAS) AF: 0.408 AC: 1962 AN: 4806

European-Finnish (FIN) AF: 0.189 AC: 1995 AN: 10560

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7096 AN: 67694

Other (OTH) AF: 0.120 AC: 252 AN: 2104

Alfa AF: 0.0614 Hom.: 62

Bravo AF: 0.141

Asia WGS AF: 0.496 AC: 1710 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.3
DANN	Benign	0.68
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12646132; hg19: chr4-80974392;